tbuckley/cabot-search huggingface dataset:
Tislelizumab plus chemotherapy for patients with<i>EGFR</i>-mutated non-squamous non-small cell lung cancer who progressed on EGFR tyrosine kinase inhibitor therapy
Authors: Hua Zhong, Xueyan Zhang, Panwen Tian, Tianqing Chu, Qisen Guo, Xinmin Yu, Zhuang Yu, Yalun Li, Lijuan Chen, Jie Liu, Yan Zhang, Yan Guan, Xun Shi, Jing Wang, Yanqiu Zhao, Baohui Han
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Treatment options are limited for epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) after treatment failure with EGFR tyrosine kinase inhibitors (TKIs). This multicenter open-label, phase II study aims to evaluate the efficacy and safety of tislelizumab plus chemotherapy (cohort 1, TIS+chemo) or tislelizumab plus chemotherapy and bevacizumab (cohort 2, TIS+chemo+ beva) in EGFR-mutated non-squamous NSCLC patients who progressed on EGFR TKI therapies. Here, the primary analysis of the TIS+chemo cohort is reported. Methods In the TIS+chemo cohort, patients with EGFR-sensitizing mutations with prior EGFR TKI failure received tislelizumab plus carboplatin and nab-paclitaxel as induction treatment, followed by maintenance with tislelizumab plus pemetrexed. The primary endpoint was 1-year progression-free survival (PFS) rate. The planned sample size was 66 with a historical control of 7%, an expected value of 20%, a one-sided α of 0.05, and a power of 85%. Results Between July 11, 2020 and December 13, 2021, 69 patients were enrolled. As of June 30, 2022, the median follow-up was 8.2 months. Among the 62 patients in the efficacy analysis set, estimated 1-year PFS rate was 23.8% (90% CI 13.1% to 36.2%), and its lower bound of 90% CI was higher than the historical control of chemotherapy (7%), which met the primary endpoint. The median PFS was 7.6 (95% CI 6.4 to 9.8) months. Median overall survival (OS) was not reached (95% CI 14.0 to not estimable), with a 1-year OS rate of 74.5% (95% CI 56.5% to 86.0%). The objective response rate and disease control rate were 56.5% (95% CI 43.3% to 69.0%) and 87.1% (95% CI 76.1% to 94.3%), respectively. Patients who had progressed on first-generation/second-generation and third-generation EGFR-TKIs at baseline had shorter PFS than those who progressed on first-generation/second-generation EGFR-TKIs (median 7.5 vs 9.8 months, p=0.031). Patients with positive ctDNA had shorter PFS (median 7.4 vs 12.3 months, p=0.031) than those with negative ctDNA. No grade 5 treatment-emergent adverse events (TEAEs) were observed. Grades 3–4 TEAEs occurred in 40.6% (28/69) of patients. Grades 3–4 immune-related AEs occurred in 5 (7.2%) patients. Conclusion The study met the primary endpoint for the TIS+chemo cohort. Tislelizumab plus chemotherapy is effective with an acceptable safety profile for EGFR -mutated non-squamous NSCLC after EGFR TKI failure.
Nested star-shaped objects segmentation using diameter annotations
Authors: Robin Camarasa, Hoel Kervadec, M. Eline Kooi, Jeroen Hendrikse, Paul J. Nederkoorn, Daniel Bos, Marleen de Bruijne
Journal: Medical Image Analysis (2023)

Most current deep learning based approaches for image segmentation require annotations of large datasets, which limits their application in clinical practice. We observe a mismatch between the voxelwise ground-truth that is required to optimize an objective at a voxel level and the commonly used, less time-consuming clinical annotations seeking to characterize the most important information about the patient (diameters, counts, etc.). In this study, we propose to bridge this gap for the case of multiple nested star-shaped objects (e.g., a blood vessel lumen and its outer wall) by optimizing a deep learning model based on diameter annotations. This is achieved by extracting in a differentiable manner the boundary points of the objects at training time, and by using this extraction during the backpropagation. We evaluate the proposed approach on segmentation of the carotid artery lumen and wall from multisequence MR images, thus reducing the annotation burden to only four annotated landmarks required to measure the diameters in the direction of the vessel's maximum narrowing. Our experiments show that training based on diameter annotations produces state-of-the-art weakly supervised segmentations and performs reasonably compared to full supervision. We made our code publicly available at https://gitlab.com/radiology/aim/carotid-artery-image-analysis/nested-star-shaped-objects.
Combined inhibition of surface CD51 and γ-secretase-mediated CD51 cleavage improves therapeutic efficacy in experimental metastatic hepatocellular carcinoma
Authors: Jianye Cai, Jiancheng Wang, Chenhao Jiang, Linsen Ye, Xinyi He, Jianyang Huang, Xiang Sun, Zhijun Ren, Xiaofan Lai, Yuan Qiu, Hongmiao Wang, Guo Lv, Jun Zheng, Tongyu Lu, Haitian Chen, Yasong Liu, Huaxin Chen, Yuanjun Guan, Yi Wang, Tao Wang, Jia Yao, Xin Sui, Yinqian Kang, Yingcai Zhang, Hua Li, Jinkai Wang, Weiqiang Li, Guihua Chen, Yang Yang, Andy Peng Xiang
Journal: Journal of Hepatology (2023)
Modelling the continuum of serious traffic injuries in police-hospital linked data by applying the random parameters hazard-based duration model
Authors: Khalid Alzaffin, Sherrie-Anne Kaye, Angela Watson, Md Mazharul Haque
Journal: Analytic Methods in Accident Research (2023)

Injury severity in police crash reports is usually recorded in three to five classes, including property damage, slight, moderate, serious, and fatal injuries. Among these classifications, serious injuries are commonly classified as cases where a road user is admitted to a hospital. In this classification, the length of hospital stay is not differentiated, whether one day or ten days, as long as the road user has been admitted to the hospital. As such, the inferences drawn from assuming that all serious injuries (1 if a road user is admitted to the hospital; 0 otherwise) are at the same severity level inherently suffer from aggregation bias and may not provide a thorough understanding of this severity category. This study proposes a hazard-based duration modelling approach to examine the severity of serious injury crashes measured in a continuous spectrum. Specifically, using the length of hospital stay as the measure of serious injuries, a random parameters hazard-based duration model with heterogeneity in means was applied to model serious injury crashes obtained by linking crash records in police and hospital databases. To address temporal instability, the injury records sources from Abu Dhabi, United Arab Emirates (UAE), between 2015 and 2019 were modelled separately for each year. The results showed that factors positively associated with more serious injury severity (prolonged length of hospital stay) are rural areas, high posted speed limits of 100–160 km/h, overturned crashes, speeding, impaired driving, involvements of a heavy vehicle, nighttime crashes, lack of restraint usage, and injuries to the head or lower extremities. In particular, speeding violations during nighttime are positively associated with more serious injuries. Furthermore, the means of the random parameters of head injury are positively influenced by speeding, lack of restraint usage, and motorcycle involvement through the heterogeneity-in-mean specification of the hazard-based duration model. The proposed modelling approach to model serious traffic injuries using a hazard-based duration model provides a comprehensive understanding of the factors associated with serious injuries.
Global prevalence of poor sleep quality in military personnel and veterans: A systematic review and meta-analysis of epidemiological studies
Authors: Wei Bai, Zhen Gui, Meng-Yi Chen, Qinge Zhang, Mei Ieng Lam, Tong Leong Si, Wan-Ying Zheng, Yu-Fei Liu, Zhaohui Su, Teris Cheung, Todd Jackson, Xiao-Hong Li, Yu-Tao Xiang
Journal: Sleep Medicine Reviews (2023)
Development of exosome membrane materials-fused microbubbles for enhanced stability and efficient drug delivery of ultrasound contrast agent
Authors: Yongho Jang, Jeehun Park, Pilsu Kim, Eun-Joo Park, Hyungjin Sun, Yujin Baek, Jaehun Jung, Tai-kyong Song, Junsang Doh, Hyuncheol Kim
Journal: Acta Pharmaceutica Sinica B (2023)

Lipid-coated microbubbles are widely used as an ultrasound contrast agent, as well as drug delivery carriers. However, the two main limitations in ultrasound diagnosis and drug delivery using microbubbles are the short half-life in the blood system, and the difficulty of surface modification of microbubbles for active targeting. The exosome, a type of extracellular vesicle, has a preferentially targeting ability for its original cell. In this study, exosome-fused microbubbles (Exo-MBs) were developed by embedding the exosome membrane proteins into microbubbles. As a result, the stability of Exo-MBs is improved over the conventional microbubbles. On the same principle that under the exposure of ultrasound, microbubbles are cavitated and self-assembled into nano-sized particles, and Exo-MBs are self-assembled into exosome membrane proteins-embedded nanoparticles (Exo-NPs). The Exo-NPs showed favorable targeting properties to their original cells. A photosensitizer, chlorin e6, was loaded into Exo-MBs to evaluate therapeutic efficacy as a drug carrier. Much higher therapeutic efficacy of photodynamic therapy was confirmed, followed by cancer immunotherapy from immunogenic cell death. We have therefore developed a novel ultrasound image-guided drug delivery platform that overcomes the shortcomings of the conventional ultrasound contrast agent and is capable of simultaneous photodynamic therapy and cancer immunotherapy.
Identification of cow milk epitopes to characterize and quantify disease-specific T cells in allergic children
Authors: Sloan A. Lewis, Aaron Sutherland, Ferran Soldevila, Luise Westernberg, Minori Aoki, April Frazier, Synaida Maiche, Mich Erlewyn-Lajeunesse, Hasan Arshad, Stephanie Leonard, Susan Laubach, Jennifer A. Dantzer, Robert A. Wood, Alessandro Sette, Gregory Seumois, Pandurangan Vijayanand, Bjoern Peters
Journal: Journal of Allergy and Clinical Immunology (2023)
Functional immunophenotyping of blood neutrophils identifies novel endotypes of viral response in preschool children with recurrent wheezing
Authors: Anne M. Fitzpatrick, Ahmad F. Mohammad, Min Huang, Susan T. Stephenson, James Patrignani, Rishikesan Kamaleswaran, Jocelyn R. Grunwell
Journal: Journal of Allergy and Clinical Immunology (2023)
Evaluation of the contribution of shotgun metagenomics in the microbiological diagnosis of liver abscesses
Authors: Hadrien Kimseng, Geoffrey Rossi, Maxime Danjean, Bryan Jimenez-Araya, Camille Chaligne, Adrien Galy, Bérénice Souhail, Frédéric Bert, Véronique Leflon, Vincent Fihman, Amandine Caillault, Vanessa Demontant, Sarah Seng, Elisabeth Trawinski, Melissa N.’Debi, Laure Boizeau, Hervé Jacquier, Maxime Ronot, Edouard Reizine, Vincent Le Roy, Agnès Lefort, Christophe Rodriguez, Raphaël Lepeule, Paul-Louis Woerther
Journal: Journal of Infection (2023)
Pharmacokinetics/pharmacodynamics of epinephrine after single and repeat administration of neffy, EpiPen, and manual intramuscular injection
Authors: Thomas B. Casale, Anne K. Ellis, Anna Nowak-Wegrzyn, Michael Kaliner, Richard Lowenthal, Sarina Tanimoto
Journal: Journal of Allergy and Clinical Immunology (2023)

Epinephrine is the first-line treatment for severe allergic reactions, and rapid treatment is associated with lower rates of hospitalization and death. Current treatment options (epinephrine auto-injectors and manual intramuscular injection) are considered cumbersome, and most patients/caregivers fail to use them, even during severe reactions. An intranasal epinephrine delivery device, neffy, has been designed to provide an additional option for patients/caregivers.
A multicenter retrospective cohort analysis of advanced basal cell carcinoma outcomes by sex
Authors: Morgan Groover, Neha Gupta, Emily Granger, Fadi Murad, Vernon J. Forrester, Emily J. Anstadt, William Su, Lauren Heusinkveld, John N. Lukens, Ann W. Silk, Jonathan D. Schoenfeld, Shlomo A. Koyfman, Emily S. Ruiz, Allison T. Vidimos
Journal: Journal of the American Academy of Dermatology (2023)
Management of Anaerobic Infections
Authors: SYDNEY M. FINEGOLD
Journal: Annals of Internal Medicine (1975)

Anaerobic infections are reviewed with emphasis on management. Most anaerobic pulmonary infections respond to penicillin G, even when Bacteroides fragilis (penicillin-resistant) is present. Clindamycin is suitable in penicillin-sensitive patients. Intraabdominal infections have a complex flora usually involving anaerobes, especially B. fragilis. It is desirable to use antimicrobial therapy to cover potential pathogens of all types. Surgical drainage and debridement are extremely important considerations. Anaerobic bacteria were found in 72% of 200 patients with female genital tract infections and were the exclusive isolates in 30%. Surgical therapy is primary, but antimicrobial and anticoagulant therapy are also important. A variety of soft-tissue infections involve anaerobes. Surgery is the major therapeutic approach. Anaerobic endocarditis is uncommon but may be difficult to manage. Chloramphenicol is ordinarily the drug of choice for brain abscess. New antimicrobial agents, which are under investigation and are promising, include new penicillins, new cephalosporins, new tetracyclines, and metronidazole.
The Role of Thyroid Hormones in Prenatal and Neonatal Neurological Development—Current Perspectives
Authors: SUSAN P. PORTERFIELD, CHESTER E. HENDRICH
Journal: Endocrine Reviews (1993)

FOR YEARS thyroid hormones have been known to be important for normal neonatal brain development, and numerous reviews have covered this topic in depth. It now also appears that fetal thyroid hormones play an essential role in fetal brain development. In addition, as some placental transport of thyroid hormones has been shown to occur, it is possible that maternal thyroid hormones might influence fetal brain development. Animal models have been used to study the influence of thyroid hormones on neurological] evelopment. Rats and mice have been the primary animals studied; however, a significant amount of data have come from studies on sheep and nonhuman primates. While the merit of application of animal data to human problems is frequently questioned, valuable information can be obtained when the animal data are properly interpreted. Furthermore, most of the information obtained from animal experiments would be unavailable from humans.
The epidemiology of skin cancer
Authors: T.L. Diepgen, V. Mahler
Journal: British Journal of Dermatology (2002)

Journal Article The epidemiology of skin cancer Get access T.L. Diepgen, T.L. Diepgen Department of Clinical Social Medicine and Dermato‐Epidemiology, University Hospital Heidelberg, Bergheimer Str. 58, 69115 Heidelberg, Germany *Department of Dermatology, University of Erlangen, Hartmann Str. 14, D‐91054, Erlangen, Germany T.L.Diepgen MD PhD. E‐mail: thomas.diepgen@med.uni‐heidelberg.de Search for other works by this author on: Oxford Academic Google Scholar V. Mahler V. Mahler Department of Clinical Social Medicine and Dermato‐Epidemiology, University Hospital Heidelberg, Bergheimer Str. 58, 69115 Heidelberg, Germany *Department of Dermatology, University of Erlangen, Hartmann Str. 14, D‐91054, Erlangen, Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 146, Issue s61, 1 April 2002, Pages 1–6, https://doi.org/10.1046/j.1365-2133.146.s61.2.x Published: 01 April 2002
Management of Hemochromatosis
Authors: James C. Barton
Journal: Annals of Internal Medicine (1998)

The complications of iron overload in hemochromatosis can be avoided by early diagnosis and appropriate management.Therapeutic phlebotomy is used to remove excess iron and maintain low normal body iron stores, and it should be initiated in men with serum ferritin levels of 300 µg/L or more and in women with serum ferritin levels of 200 µg/L or more, regardless of the presence or absence of symptoms. Typically, therapeutic phlebotomy consists of 1) removal of 1 unit [450 to 500 mL] of blood weekly until the serum ferritin level is 10 to 20 µg/L and 2) maintenance of the serum ferritin level at 50 µg/L or less thereafter by periodic removal of blood. Hyperferritinemia attributable to iron overload is resolved by therapeutic phlebotomy. When applied before iron overload becomes severe, this treatment also prevents complications of iron overload, including hepatic cirrhosis, primary liver cancer, diabetes mellitus, hypogonadotrophic hypogonadism, joint disease, and cardiomyopathy. In patients with established iron overload disease, weakness, fatigue, increased hepatic enzyme concentrations, right upper quadrant pain, and hyperpigmentation are often substantially alleviated by therapeutic phlebotomy. Patients with liver disease, joint disease, diabetes mellitus and other endocrinopathic abnormalities, and cardiac abnormalities often require additional, specific management. Dietary management of hemochromatosis includes avoidance of medicinal iron, mineral supplements, excess vitamin C, and uncooked sea-foods. This can reduce the rate of iron reaccumulation; reduce retention of nonferrous metals; and help reduce complications of liver disease, diabetes mellitus, and Vibrio infection. This comprehensive approach to the management of hemochromatosis can decrease the frequency and severity of iron overload, improve quality of life, and increase longevity.
Risk Factors for Cerebral Edema in Children with Diabetic Ketoacidosis
Authors: Nicole Glaser, Peter Barnett, Ian McCaslin, David Nelson, Jennifer Trainor, Jeffrey Louie, Francine Kaufman, Kimberly Quayle, Mark Roback, Richard Malley, Nathan Kuppermann
Journal: New England Journal of Medicine (2001)

Cerebral edema is an uncommon but devastating complication of diabetic ketoacidosis in children. Risk factors for this complication have not been clearly defined.
Relapsing Polychondritis
Authors: Carl M. Pearson, Henry M. Kline, Victor D. Newcomer
Journal: New England Journal of Medicine (1960)

TWO cases of an allegedly rare disease have been seen by us within the past several months. In each an intense inflammatory and degenerative process developed in several cartilaginous structures that were eventually dissolved and replaced by fibrous connective tissue. Because of its episodic nature we have called this syndrome relapsing polychondritis. In the 10 cases reported in the literature to date1 2 3 4 5 6 7 8 9 10 11 this condition has been known as polychondropathy,1 systemic chondromalacia2 and chronic atrophic polychondritis11 and also by several descriptive titles. None of the designations, including our own, completely fit the picture of the disease, for in addition to . . .
P431: ACTIVATION OF MACROPHAGE STING ENHANCES PHAGOCYTOSIS OF ACUTE MYELOID LEUKAEMIA
Authors: Rebecca Maynard, Charlotte Hellmich, Katherine Hampton, Jamie Moore, Aisha Jibril, Ravindu De Silva, Dominic Fowler-Shorten, Martha Ehikioya, Kristian Bowles, Stuart Rushworth
Journal: HemaSphere (2023)

Background: Acute myeloid leukaemia (AML) initiation, expansion and treatment resistance is regulated by interactions with the bone marrow (BM) microenvironment. Previous research by our group has shown that AML activates macrophage phagocytosis via activation of the stimulator of interferon genes (STING) pathway. This is in contrast to solid tumours where immunosuppressive signals are released by infiltrating macrophages and enhances tumour progression. Phagocytosis of AML blasts can be mitigated by the interaction of CD47, on AML blasts, with SIRPα on BM macrophages, causing a ‘don’t eat me’ signal. Recent studies into this have led to clinical trials evaluating the therapeutic potential of blocking CD47 in patients with AML suppression (NCT04980885). Aims: We aim to determine whether activation of the STING pathway, by agonists, enhances phagocytic activity of BM macrophages and if so, does this supress AML expansion. We further aim to investigate if STING agonists can be used in combination with anti-CD47 blockade, to increase AML clearance. Methods: Bone marrow derived macrophages (BMDM) were stimulated with STING pathway agonists DMXAA and cGAMP, followed by qPCR to assess the activation of STING associated genes. qPCR was also performed on macrophages, isolated by FACS (GR1-, F4/80+/ CD115int), from C57Bl/6 mice treated with the agonists. Next BMDM were cocultured with pHrodo BioParticles or established AML cell lines (MN1 or HOXA0/Meis1) and treated with the STING agonists and/or anti-CD47 to investigate whether improved AML removal could be achieved with the combination treatment. Quantification was performed by cell counts and flow cytometry. C57Bl/6 mice were engrafted with MN1 or HOXA0/Meis1 AML cells and treated with DMXAA and/or anti-CD47. Mice were monitored every day to assess whether treatment improved survival. Results: STING agonists induced a STING gene expression signature (upregulation of GBP, IFIT3 and IRF3) in vitro (BMDM) and in vivo (FACS isolated BM macrophages), upon assessment using qPCR. Cell counts and flow cytometry showed that STING agonists induced the phagocytosis of AML by BMDM in a coculture system. In vivo, mice receiving the STING agonist DMXAA had significantly improved survival over controls. The addition of anti-CD47 blockade saw no improved AML removal in vitro. However, in vivo the combined treatment of DMXAA and anti-CD47 resulted in significant extended survival over DMXAA treated mice. Summary/Conclusion: In summary we report that STING activated BM macrophages suppress AML growth via phagocytosis. This process is further enhanced when blocking CD47 on AML blasts. These results provide rationale to investigate the clinical potential of targeting STING and CD47 in combination for the treatment of AML. Keywords: Macrophage, Acute myeloid leukemia, Phagocytosis
Pulmonary Tuberculosis in HIV-Infected Patients in Zaire — A Controlled Trial of Treatment for Either 6 or 12 Months
Authors: Joseph H. Perriëns, Michael E. St. Louis, Yiadiul B. Mukadi, Christopher Brown, Jacques Prignot, Françoise Pouthier, Françoise Portaels, Jean-Claude Willame, Justin K. Mandala, Mulamba Kaboto, Robert W. Ryder, Giorgio Roscigno, Peter Piot
Journal: New England Journal of Medicine (1995)

We studied the efficacy of a short-course regimen of chemotherapy for pulmonary tuberculosis in Kinshasa, Zaire. We also assessed whether, among patients with human immunodeficiency virus (HIV) infection, treatment should be extended from 6 to 12 months.
Idarucizumab for Dabigatran Reversal
Authors: Charles V. Pollack, Paul A. Reilly, John Eikelboom, Stephan Glund, Peter Verhamme, Richard A. Bernstein, Robert Dubiel, Menno V. Huisman, Elaine M. Hylek, Pieter W. Kamphuisen, Jörg Kreuzer, Jerrold H. Levy, Frank W. Sellke, Joachim Stangier, Thorsten Steiner, Bushi Wang, Chak-Wah Kam, Jeffrey I. Weitz
Journal: New England Journal of Medicine (2015)

Specific reversal agents for non–vitamin K antagonist oral anticoagulants are lacking. Idarucizumab, an antibody fragment, was developed to reverse the anticoagulant effects of dabigatran.
Rhinosinusitis: Developing guidance for clinical trials
Authors: Eli O. Meltzer, Daniel L. Hamilos, James A. Hadley, Donald C. Lanza, Bradley F. Marple, Richard A. Nicklas, Allen D. Adinoff, Claus Bachert, Larry Borish, Vernon M. Chinchilli, Melvyn R. Danzig, Berrylin J. Ferguson, Wytske J. Fokkens, Stephen G. Jenkins, Valerie J. Lund, Mahmood F. Mafee, Robert M. Naclerio, Ruby Pawankar, Jens U. Ponikau, Mark S. Schubert, Raymond G. Slavin, Michael G. Stewart, Alkis Togias, Ellen R. Wald, Birgit Winther
Journal: Journal of Allergy and Clinical Immunology (2006)